Persistent relegated numbers and gene expression of NK cells acts as a sensor of Long-Term COVID-19 Syndrome (LTCS)

Independent of the severity of the infection incidence, approximately 10-20% of all individuals who recovered SARS-CoV2 infection had persistent COVID-19 like symptoms more than 12 weeks and this was termed as Long-Term COVID19 Syndrome (LTCS) or Long COVID. However, how these persistent symptoms lasts is still widely unclear and understanding the mechanisms behind that causes needs utmost consideration. We identified that the mean anti-Spike S1 antibody IgG titres in plasma tended to be higher in LTCS patients compared to convalescent control (COV) individuals after 12 weeks of infection. Surprisingly, most of the inflammatory (IFN-g, TNF-a, IL-6) and anti-inflammatory cytokines (IL-10) levels were lower compared to COV or healthy control (HC) individuals. We characterized the cellular immune response using 14-color flow cytometry based immunophenotyping and validated by single cell RNA-sequencing at cellular and gene levels. We identified that NK cells were reduced and their functions at molecular level were compromised in LTCS patients. Most interesting, although investigating blood as a tissue, gene pathways associated with taste and smell were suppressed in LTCS compared with CONV or HC. Our study highlights a potential mechanism how dysregulated humoral and cellular immunity plays an important role in the development of Long COVID in patients.